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酪蛋白激酶1δ的沉默降低三阴性乳腺癌细胞的迁移和转移。

Silencing of casein kinase 1 delta reduces migration and metastasis of triple negative breast cancer cells.

作者信息

Bar Isabelle, Merhi Ahmad, Larbanoix Lionel, Constant Manuel, Haussy Sandy, Laurent Sophie, Canon Jean-Luc, Delrée Paul

机构信息

Laboratory of Translational Oncology, Institute of Pathology and Genetics/Grand Hôpital de Charleroi, Gosselies 6041, Belgium.

IPG BioBank, Institute of Pathology and Genetics, Gosselies 6041, Belgium.

出版信息

Oncotarget. 2018 Jul 20;9(56):30821-30836. doi: 10.18632/oncotarget.25738.

Abstract

The casein kinase 1 delta (CSNK1D) is a conserved serine/threonine protein kinase that regulates diverse cellular processes including cell cycle progression, circadian rhythm, and neurite outgrowth. Aberrant expression of CSNK1D is described in several cancer types including breast cancer, where it is amplified in about 30% of triple negative breast (TNBC). Here, we have investigated the function of CSNK1D in triple negative cancer cell migration and metastasis. By using immunohistochemistry and hybridization, we found that CNSK1D is highly expressed in primary tumor cells and in tumor cells invading lymphatic nodes compared to non-metastatic tumors. , knock-down of expression with specific shRNAs in the breast cancer cell line MDA-MB-231 markedly inhibited cancer cell proliferation, invasion and migration and affected the expression of the tight junction proteins claudin 1, occludin and the junction adhesion molecule A. , the inactivation of reduced lung metastasis in MDA-MB-231 breast cancer xenografts. Altogether, our results indicate that the downregulation of CSNK1D expression inhibits the proliferation and reduces the migration and the metastasis of breast cancer cells. As numerous inhibitors of CSNK1D are currently under development, this might represent an attractive therapeutic target for the treatment of TNBC.

摘要

酪蛋白激酶1δ(CSNK1D)是一种保守的丝氨酸/苏氨酸蛋白激酶,可调节多种细胞过程,包括细胞周期进程、昼夜节律和神经突生长。在包括乳腺癌在内的几种癌症类型中都描述了CSNK1D的异常表达,在三阴性乳腺癌(TNBC)中约30%存在该基因扩增。在此,我们研究了CSNK1D在三阴性癌细胞迁移和转移中的功能。通过免疫组织化学和杂交技术,我们发现与非转移性肿瘤相比,CNSK1D在原发性肿瘤细胞和侵袭淋巴结的肿瘤细胞中高表达。在乳腺癌细胞系MDA-MB-231中,用特异性短发夹RNA敲低其表达可显著抑制癌细胞增殖、侵袭和迁移,并影响紧密连接蛋白claudin 1、occludin和连接粘附分子A的表达。此外,CSNK1D的失活减少了MDA-MB-231乳腺癌异种移植模型中的肺转移。总之,我们的结果表明,CSNK1D表达下调可抑制乳腺癌细胞的增殖,并减少其迁移和转移。由于目前正在开发多种CSNK1D抑制剂,这可能是治疗TNBC的一个有吸引力的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eccf/6089398/40ae3973e43b/oncotarget-09-30821-g001.jpg

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